This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. HUMAN STUDIES- T. Kiser, MD This project is a human research study on subjects with spinal cord injury (SCI) aimed at establishing the optimal treatment strategies testing the effects of a passive motorized bicycle exercise program conducted in the individuals'homes. This Project will assess the effects of this therapy in improving neurologic recovery and decreasing secondary complications. We have designed a motorized bicycle exercise trainer (MBET) that can be used in the home and are developing a way to measure for compliance and other measures of use. The main hypothesis to be tested is that long-term MBET will increase muscle mass, reduce hyperreflexia and spasticity, as well as reduce the complications common to SCI. Specific Aim 1: We will measure and compare changes in leg muscle mass measured by MRI in groups of 2 "Chronic" (greater than one year after injury) patients who will undergo MBET for 25 weeks. These studies will determine if long-term MBET has salutary effects on muscle mass. After the end of testing, we will stop MBET and measure muscle mass to determine salutary effects, then again 12 weeks later to determine regression or savings in muscle mass. Every 6 months, another group of 2 patients will begin MBET for a total of 8 Chronic patients. An equal number of Chronic control SCI patients will be tested. Specific Aim 2: The use of MBET was found also to increase habituation of the H-reflex (the electrophysiological equivalent of the ankle reflex), and may thus offer relief from hyperreflexia. We will test the effects of MBET for changes in H-reflex habituation, spasticity measures, and a potential decrease in the amount of baclofen needed to reduce spasticity in the same groups of "Chronic" SCI patients. These studies will determine if MBET has differential effects on the modulation of spinal circuitry mediating reflex behavior. Each group of subjects in Aim 1 will be tested every 2 to 4 weeks for H-reflex and spasticity/baclofen changes during the 25-week test period, and also during the 12-week post-MBET period. These data will reveal levels of regression or savings in reflex and spasticity measures resulting from MBET therapy. Specific Aim 3: The secondary complications of pressure sores, pain, osteoporosis, bowel impactions and recurrent bladder infections are common in SCI. We will assess the medical history of these complications, conduct a physical exam to assess for pressure sores before and after MBET, and conduct a DEXA scan to assess for osteoporosis before and after the MBET program to determine its effect on osteoporosis. Specific Aim 4: Recruit one "Acute" subject every 6 months from the SCI service at our rehabilitation hospital to participate in an acute SCI MBET protocol. The aim is to institute MBET within 4-6 weeks after injury (before hyperreflexia and significant muscle atrophy sets in), and monitor H-reflex, spasticity scores and secondary complications for 25 weeks, then stop MBET but monitor all measures for 12 weeks to determine regression or savings. An equal number of Acute control subjects will be tested. These subjects will be tested at two-week intervals until reflexes stabilize. ANIMAL STUDIES- N.B. Reese, PT, PhD The long-term goal of Project IV is to develop a Spinal Cord Injury (SCI) Mobilization Program for increasing the quality of life of SCI victims. We have designed parallel human and animal studies aimed at establishing the optimal treatment strategies for regaining certain functions, testing the effects of different therapies in humans while exploring novel potential palliative strategies on animals. The animal studies have focused on the effects of passive exercise, in the form of motorized bicycle exercise training (MBET), on low-frequency depression of the H-reflex (hyperreflexia) in rats following spinal cord transection. The effects of MBET on low-frequency depression of the H-reflex have been tested following initiation of exercise in acutely transected and chronically transected animals. In addition, we have examined the residual effects of exercise on the H-reflex once the exercise intervention is terminated. This Project is allowing us to assess the effects of both "early" rehabilitation efforts and "late" rehabilitation efforts in improving neurologic recovery and decreasing secondary complications such as hyperreflexia.